In a landmark study published in Nature Aging in October 2025, a multi-institutional team led by researchers at the Nestlé Institute of Health Sciences and the École Polytechnique Fédérale de Lausanne (EPFL) has identified two common dietary compounds—thymol and carvacrol—as novel geroprotectors. Unlike existing longevity interventions that typically target nutrient sensing pathways (such as mTOR or AMPK) directly, these herbal terpenoids appear to function through a distinct bioenergetic mechanism: transient mitochondrial uncoupling.
The research, titled “Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging” 1, provides a rigorous, multi-species validation of these compounds. From high-throughput screening in zebrafish to genetic confirmation in Caenorhabditis elegans and phenotypic validation in senescence-accelerated (SAMP8) and diet-induced obesity mouse models, the data suggests a conserved mechanism of action. The compounds trigger a mild, transient depolarization of the mitochondrial membrane potential, which acts as a hormetic stress signal to activate the PINK1-Parkin mitophagy pathway. This selective clearance of dysfunctional mitochondria resulted in reduced liver steatosis, preserved muscle function (sarcopenia prevention), and a measurable delay in epigenetic aging.2
This report provides an exhaustive analysis of these findings, designed specifically for the scientifically literate longevity biohacker. It integrates the mechanistic nuances of the discovery with broader geroscience concepts—including the cGAS-STING inflammatory pathway and endothelial health—and offers a translational roadmap for N=1 experimentation, covering dosage, sourcing, and biomarkers.
Detailed Gemini Research Paper analysis: https://gemini.google.com/share/1c4ae08cb1af
Source Research Paper (open access): Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging
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Great minds think alike
I was also searching up some similar information, but also looking at dosing:
Here is my prompt:
From what foods and / or supplements are the compounds Thymol and Carvacrol typically obtained? What might be the target dosing levels for translating the data in this study to human applications?
Gemini Response:
Based on the data from the Nature Aging paper (Civiletto et al., 2025) and standard pharmacological conversion standards, here is the breakdown of sources and target dosing for human application.
1. Sources of Thymol and Carvacrol
While these compounds are present in common culinary herbs, the concentrations required to trigger the specific mitochondrial “uncoupling” effect observed in the study are difficult to achieve through diet alone.
Primary Dietary Sources:
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Thyme (Thymus vulgaris): The primary source of Thymol.
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Concentration: Dried thyme typically contains 1% to 2.5% essential oil by weight, of which 40–60% is thymol.[1]
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Math: 1 gram of dried thyme provides approximately 5 mg of thymol.
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Oregano (Origanum vulgare): The primary source of Carvacrol.
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Concentration: Dried oregano is generally higher in essential oils (up to 4%), predominantly carvacrol (60–80% of the oil).[2]
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Math: 1 gram of dried oregano provides approximately 15–20 mg of carvacrol.
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Other Sources: Wild Bergamot (Monarda fistulosa), Ajowan seeds (Trachyspermum ammi - very high thymol content), and Savory (Satureja).
Supplement Sources:
To reach therapeutic levels without consuming excessive amounts of plant matter, standardized extracts are the practical choice:
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Oregano Oil Softgels: widely available, often standardized to 55–75% Carvacrol.
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Thyme Oil Softgels: Less common but available, usually marketed for respiratory health.
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Essential Oils (Liquid): Highly concentrated, but must be diluted in a carrier oil (e.g., olive oil) before internal consumption to prevent mucosal burns.
2. Target Dosing for Longevity Translation
The researchers used a specific dosing protocol in mice to achieve the reduced liver fat, sarcopenia prevention, and delayed epigenetic aging.
The Animal Dose:
The study administered 20 mg/kg of pure thymol via oral gavage to the mice.[3]
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Frequency: 5 days per week.
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Duration: 12 weeks (chronic treatment).
Human Equivalent Dose (HED):
To translate this to humans, we use allometric scaling based on Body Surface Area (BSA). The standard conversion factor from mouse to human is 0.081 (or dividing the mouse dose by 12.3).
$$20 \text{ mg/kg (Mouse)} \times 0.081 \approx \mathbf{1.62 \text{ mg/kg (Human)}}$$
Calculated Human Daily Targets:
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60 kg (132 lbs): ~97 mg
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70 kg (154 lbs): ~113 mg
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80 kg (176 lbs): ~130 mg
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90 kg (198 lbs): ~146 mg
The “Biohacker” Protocol:
Based on these calculations, a target daily intake of 100–150 mg of total terpenoids (Thymol + Carvacrol) appears to be the translational “sweet spot.”
3. Practical Implementation & Reality Check
Food vs. Supplements:
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Dietary Difficulty: To get ~115 mg of actives from food, you would need to consume approximately 20+ grams of dried thyme or 6–8 grams of dried oregano daily. This is a massive volume (half a standard spice jar) and is likely impractical for most people.
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Supplement Approach: A standard Oregano Oil softgel often contains 30–50 mg of Carvacrol.
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Protocol: 2–3 softgels of a high-potency standardized oil would hit the target HED.
Important Protocol Nuances:
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Pulsed Dosing: The mice were dosed 5 days per week.[3] This is critical for two reasons:
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Antimicrobial Impact: Thymol and Carvacrol are potent antimicrobials. Continuous daily use could disrupt the gut microbiome. Taking “weekends off” may allow the microbiome to recover.
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Mitochondrial Hormesis: The mechanism is “transient uncoupling.” Constant uncoupling might lead to mitochondrial fatigue. The pause allows the system to reset and adapt.
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Timing: The study notes that the mitochondrial depolarization is transient.[4, 5] Taking the dose in the morning or during a fasting window might synergize with natural autophagic rhythms.
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I like these essential oils which are isomers with a form of antibiotic effect. However I would want to study the uncoupling in some detail to ensure it did not target the wrong mitochondria.
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Let us know what you find… Yes, this is really an interesting and new area, it seems.
I have in the past used these EOs to deal with infection.
Looking at the paper it appears that the there is no lifespan extension in C. elegans although the mouse experiments did not last for long enough to test lifespan. Hence it appears that this increases mito/autophagy, but is not as selective as one would wish. Hence although I will keep an eye on future results with these I am not inclined to try them myself.
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